Background The value of adjuvant systemic therapy after margin-negative resection for gastric gastrointestinal stromal tumors (GISTs) remains unclear. Methods The National Cancer Data Base was queried to identify patients undergoing margin negative resections for gastric GISTs >2 cm between 2010 and 2015. Patients were stratified by tumor size (small: 2.1–5 cm, intermediate: 5.1–10 cm, large: >10 cm), histologic grade (low: ≤5 mitoses/50 HPF and high: >5 mitoses/50 HPF), and use of adjuvant therapy. Multivariable cox proportional hazard methods were used to compare overall survival (OS). Results 3520 patients met inclusion criteria. Adjuvant therapy was associated with a statistical improvement in OS (86% vs. 76%, p = 0.014) for those with large tumors but had no measurable effect in patients with small or intermediate sized tumors. On multivariable analysis, this association was independent of grade. Conclusions Adjuvant therapy is associated with improved OS for patients with gastric GISTs >10 cm but provides no statistically significant benefit in OS for those with GISTs 2–10 cm